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Pathologies liées aux déficits du cycle de Krebs

Published on Apr 1, 2018in Revue Francophone Des Laboratoires
· DOI :10.1016/s1773-035x(18)30120-5
Paule Bénit35
Estimated H-index: 35
(French Institute of Health and Medical Research),
Sylvie Bortoli7
Estimated H-index: 7
(Paris Descartes University)
+ 2 AuthorsPierre Rustin79
Estimated H-index: 79
(French Institute of Health and Medical Research)
Resume Chez l'homme, les dysfonctions des enzymes du cycle de Krebs liees a des mutations causent des encephalopathies severes du jeune enfant, ou differents types de tumeurs et de cancers touchant differents organes. Ainsi des mutations des genes de la succinate-deshydrogenase ont ete identifiees dans des formes familiales de pheochromocytomes et paragangliomes. Les mutations du gene de la fumarase s'observent dans des leiomyomes uterins en association avec des cancers renaux, mais des cas d'encephalopathies de l'enfant ont aussi ete observes. Les mutations des genes de l'isocitrate-deshydrogenase peuvent representer jusqu'a 20% des leucemies myeloides aigues et jusqu'a 80% dans certains gliomes. On ne sait actuellement expliciter la diversite des consequences possibles de ces mutations : encephalopathies versus cancers, nature des tissus affectes, cinetique variable d'apparition des symptomes. Il semble en revanche etabli que les anomalies dans les equilibres metaboliques qui resultent de ces mutations soient a la base des processus tumoraux en modulant l'activite d'hydroxylases susceptibles d'affecter certains facteurs de transcriptions, mais aussi la methylation de l'ADN et les histones. Dans ce contexte, il semble etonnant que soient largement utilises certains fongicides dont l'effet est de bloquer une etape centrale du cycle de Krebs, la succinate-deshydrogenase. Le principe de precaution voudrait sans aucun doute de reevaluer urgemment la necessite de l'usage de telles substances pour l'homme et l'environnement.
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Published on Mar 1, 2018in Pest Management Science 3.25
Masao Yamashita1
Estimated H-index: 1
(Rothamsted Research),
B. A. Fraaije28
Estimated H-index: 28
(Rothamsted Research)
4 Citations Source Cite
Published on Oct 18, 2017in PLOS ONE 2.77
Caspar A. Hallmann7
Estimated H-index: 7
(Radboud University Nijmegen),
Martin Sorg1
Estimated H-index: 1
+ 9 AuthorsThomas Hörren1
Estimated H-index: 1
Global declines in insects have sparked wide interest among scientists, politicians, and the general public. Loss of insect diversity and abundance is expected to provoke cascading effects on food webs and to jeopardize ecosystem services. Our understanding of the extent and underlying causes of this decline is based on the abundance of single species or taxonomic groups only, rather than changes in insect biomass which is more relevant for ecological functioning. Here, we used a standardized pr...
234 Citations Source Cite
Published on Oct 1, 2017in FEBS Letters 3.00
Dylan G. Ryan5
Estimated H-index: 5
(Trinity College, Dublin),
Luke A. J. O'Neill93
Estimated H-index: 93
(Trinity College, Dublin)
The Krebs cycle is an amphibolic pathway operating in the mitochondrial matrix of all eukaryotic organisms. In response to proinflammatory stimuli, macrophages and dendritic cells undergo profound metabolic remodelling to support the biosynthetic and bioenergetic requirements of the cell. Recently, it has been discovered that this metabolic shift also involves the rewiring of the Krebs cycle to regulate cellular metabolic flux and the accumulation of Krebs cycle intermediates, notably, citrate, ...
21 Citations Source Cite
Published on Apr 1, 2017in Biochimie 3.19
Karishma Sajnani1
Estimated H-index: 1
(Griffith University),
Farhadul Islam11
Estimated H-index: 11
(Griffith University)
+ 2 AuthorsAlfred King-Yin Lam33
Estimated H-index: 33
(Griffith University)
Cancer cells exhibit alterations in many cellular processes, including oxygen sensing and energy metabolism. Glycolysis in non-oxygen condition is the main energy production process in cancer rather than mitochondrial respiration as in benign cells. Genetic and epigenetic alterations of Krebs cycle enzymes favour the shift of cancer cells from oxidative phosphorylation to anaerobic glycolysis. Mutations in genes encoding aconitase, isocitrate dehydrogenase, succinate dehydrogenase, fumarate hydr...
12 Citations Source Cite
Published on Aug 1, 2016in Neurobiology of Disease 5.23
Douglass M. Turnbull93
Estimated H-index: 93
(Newcastle University),
Pierre Rustin79
Estimated H-index: 79
(French Institute of Health and Medical Research)
Abstract The major progress made in the identification of the molecular bases of mitochondrial disease has revealed the huge diversity of their origin. Today up to 300 mutations were identified in the mitochondrial genome and about 200 nuclear genes are possibly mutated. In this review, we highlight a number of features specific to mitochondria which possibly participate in the complexity of these diseases. These features include both the complexity of mitochondrial genetics and the multiplicity...
17 Citations Source Cite
Published on May 1, 2015in Analytical and Bioanalytical Chemistry 3.31
Antonio Abad Fuentes17
Estimated H-index: 17
(Spanish National Research Council),
Eric Ceballos-Alcantarilla2
Estimated H-index: 2
(University of Valencia)
+ 3 AuthorsFrancesc A. Esteve Turrillas19
Estimated H-index: 19
(Spanish National Research Council)
In recent years, a second generation of succinate-dehydrogenase-inhibitor (SDHI) fungicides has been introduced into the market for effective treatment of fruit and vegetable crops, with fluxapyroxad, boscalid, fluopyram, penflufen, bixafen, penthiopyrad, and isopyrazam being some of the members of this new class of agrochemical. We herein report the development of an analytical procedure for the determination of residues of these SDHI fungicides in food samples, based on a modification of the Q...
20 Citations Source Cite
Published on Feb 1, 2015in Nature 41.58
Bryce W. Carey12
Estimated H-index: 12
Lydia W.S. Finley20
Estimated H-index: 20
+ 2 AuthorsCraig B. Thompson157
Estimated H-index: 157
If deprived of exogenous glutamine, naive mouse embryonic stem cells are shown to be capable of generating the amino acid from other sources to enable their proliferation; the stem cells use glutamine and glucose catabolism to maintain a high level of intracellular α-ketoglutarate and promote demethylation of chromatin and ensure sufficient expression of pluripotency-associated genes.
280 Citations Source Cite
Published on Nov 15, 2014in International Journal of Cancer 7.36
Aurélie Morin10
Estimated H-index: 10
(Paris Descartes University),
Eric Letouzé23
Estimated H-index: 23
+ 1 AuthorsJudith Favier34
Estimated H-index: 34
(Paris Descartes University)
Although the alteration of cellular metabolism in cancer was reported by Warburg in the early 1930s, a regain of interest in cancer metabolism has more recently followed the discovery of germline or somatic mutations in genes coding for metabolic enzymes (succinate dehydrogenase, fumarate hydratase and isocitrate dehydrogenase) that are associated with tumor susceptibility. Mutations in these genes are found in numerous tumor types including paragangliomas, kidney cancers, leiomyomas, glioblasto...
59 Citations Source Cite
Published on Aug 1, 2014in Biochimica et Biophysica Acta 3.44
Paule Bénit35
Estimated H-index: 35
(French Institute of Health and Medical Research),
Eric Letouzé23
Estimated H-index: 23
+ 5 AuthorsPierre Rustin79
Estimated H-index: 79
(French Institute of Health and Medical Research)
Abstract Seventy years from the formalization of the Krebs cycle as the central metabolic turntable sustaining the cell respiratory process, key functions of several of its intermediates, especially succinate and fumarate, have been recently uncovered. The presumably immutable organization of the cycle has been challenged by a number of observations, and the variable subcellular location of a number of its constitutive protein components is now well recognized, although yet unexplained. Nonethel...
25 Citations Source Cite
Published on Jun 1, 2013in Cancer Cell 22.84
Eric Letouzé23
Estimated H-index: 23
Cosimo Martinelli3
Estimated H-index: 3
(Paris Descartes University)
+ 15 AuthorsPaule Bénit35
Estimated H-index: 35
(French Institute of Health and Medical Research)
SUMMARY Paragangliomas areneuroendocrinetumorsfrequentlyassociatedwithmutationsinRET,NF1,VHL,and succinate dehydrogenase (SDHx) genes. Methylome analysis of a large paraganglioma cohort identified three stable clusters, associated with distinct clinical features and mutational status. SDHx-related tumors displayed a hypermethylator phenotype, associated with downregulation of key genes involved in neuroendocrine differentiation. Succinate accumulation in SDH-deficient mouse chromaffin cells led ...
323 Citations Source Cite
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